It’s one thing knowing that two different plants each have genes conferring specific traits of interest, says Ohalo CEO Dave Friedberg. The problem is that when you crossbreed them, a random 50% of the genes from each parent transfer to their offspring, which means the whole endeavor remains a crapshoot.
“[With traditional cross-breeding methods] it may never happen that you get all the good genes together in one plant to make it both disease resistant and drought resistant, for example. You just have to get lucky to be successful.”
California-based Ohalo, which has spent the last five years in stealth mode honing its gene editing techniques and filing patents (click here and here), effectively ensures the progeny of two plants will get all the traits of interest by ensuring that both parents pass on their entire genome to their offspring.
The ‘boosted breeding’ technology, which deploys proteins to effectively switch off the mechanism that splits the genes in each parent, is a potential gamechanger in the crop breeding world, claims Friedberg, as the resulting plants contain all the beneficial traits from both parents, rather than a random half of the traits from each parent.
Strikingly, these ‘polyploid’ plants [possessing more than two complete sets of chromosomes] have also been shown to have significantly higher yields, says the startup, which was formed in 2019 by Friedberg’s investment company and venture foundry The Production Board. Ohalo has since raised “a little over $100 million” from undisclosed investors.
‘Rather than end up with a crapshoot where we’re 50% likely to get the traits we want, we’re 100% going to get them all’
Friedberg told AgFunderNews: “I reached out to Dr. Jud Ward [Ohalo cofounder and CTO] a few years ago after reading an article in the New Yorker about Driscoll’s strawberry breeding work where Ward worked as a molecular biologist. In early 2019, we started talking again, and we set up Ohalo officially in late summer 2019. As of November last year, I joined as full-time CEO.”
In a nutshell, he said, “What we’re effectively doing is controlling the ability to create offspring through clonal gametes [‘sex cells’]. We have basically figured out how to get gametes, which are formed through a process called meiosis, to be clonal and go through mitosis, so they preserve the full genome of the mother and the full genome of the father. That allows us to take a mother with desirable traits and a father with desirable traits, and rather than end up with a crapshoot where we’re 50% likely to get the traits we want, we’re 100% going to get them all.”
He added: “The theory was, if we could do this, the hybrids would be more vigorous, healthier, and grow bigger and faster. And the answer we got is yes, in all the different plants we tried it in, as we’re significantly increasing the genetic diversity and giving the plants extra genes they can use in times of need.
“The way we’ve done it allows us to be super-efficient, super-accurate, super-fast, and super high-throughput, so that’s allowed us to launch all of these breeding programs, whereas other people will struggle for years just working on one crop. We get results right away.”
Polyploidy “is actually not that uncommon in plants,” noted Friedberg, who has started sharing Ohalo’s story more publicly this week following the publication of a couple of patents. “There is a whole bunch of plant species that are polyploid with multiple sets of chromosomes. Potatoes are tetraploid (four sets of chromosomes in each cell), strawberries are octoploid. Sometimes in evolution plants go through spontaneous polyploidy. Somehow the genes double or they end up inheriting both sets of chromosomes. What we’re effectively doing is controlling polyploidy.”
“There is definitely a holy shit moment when you speak with breeders about this. I will also tell you that we’ve met with a lot of breeders who don’t believe it, but that will change. It’s not something that we know other people have been trying to do, so we’re pretty excited.” Dave Friedberg, CEO, Ohalo
‘We’re unlocking the seed industry for crops that are vegetatively propagated’
Meanwhile, as Ohalo’s process delivers the entire genome from each of the boosted parent plants, every seed they produce is genetically identical, he said. As a result, Ohalo’s technology can enable the production of uniform seed for farmers, replacing traditional methods of vegetative propagation still used in many crop systems today. This can save both time and money.
Take potatoes, said Friedberg. They produce seeds, but they are all genetically different, so most potatoes are grown from other potatoes (‘seed potatoes’), which are cut into smaller pieces and planted.
“But with our system, because you’re getting the whole genome from the mother and the whole genome from the father, not a random 50% chance, every seed is the same,” he explained. “And so for the first time ever, we can create true potato seeds and that’s never been done before.”
He added: “The potato industry spends north of 20% of revenue on replanting potatoes and the genetics haven’t improved much in the last 100 years. We’re unlocking the seed industry in crops that are vegetatively propagated.”
Downsides?
But are there any downsides or tradeoffs to having extra genes?
“No,” claimed Friedberg. “We’re not introducing non-native DNA and these aren’t transgenic plants. We’re just bringing two native plants together. The only risk is that once you get beyond a certain limit of polyploidy, and it varies from species to species, you actually start to see yield declines. But for what we’re talking about, as far as we’ve seen, it’s universally beneficial.”
The business model
For potatoes, Ohalo plans to breed and develop potato lines and produce seeds, said Friedberg. “How we go to market will vary depending on the class of the potato and the market that we’re operating in.”
In other crops, he said, “It’s a different model. So for example, if an ag company has its own germplasm [seeds, plants, or plant parts useful in crop breeding], we can partner with them and participate in that value creation. And then in other cases, we might license out the tech but generally speaking, we want to partner across markets, regions, and crops and really accelerate the adoption of this technology.”
The ’holy shit’ moment
So how is the industry responding to Ohalo’s innovations?
There is “definitely a holy shit moment when you speak with breeders about it,” said Friedberg. “I will also tell you that we’ve met with a lot of breeders who don’t believe it, but that will change. It’s not something that we know other people have been trying to do, so we’re pretty excited.”
He added: “It’s going to take us a while to explain to people and show that it’s real. So that’s what we’re going through now… getting people to really understand it.”
Speaking on this week’s episode of the All-In Podcast—which he co-hosts with VC heavyweights David Sacks, Chamath Palihapitiya, and Jason Calacanis—Friedberg told listeners: “We’ve seen incredible yield gains in potato almost overnight. Some of the data we have is ridiculous. The yield on some of these plants goes up by 60% to 100% or more.”
He added: “We’re going to be applying this boosting technology across nearly every major crop worldwide. It’ll both increase yield but it will also have a massive impact on the ability to deliver seeds, help farmers, and lower food prices.”
As for where artificial intelligence comes in, he said: “There’s a lot of work going on now in what’s called quantitative genomics, where you look at the statistics across all the genes, you use a model, and the model predicts which two crosses you want to make out of hundreds of thousands or millions of potential crosses. The AI predicts, here’s the two best ones to cross.”
According to public submissions to USDA, traits Ohalo has been looking at in potatoes include higher levels of beta-carotene, and lower levels of reducing sugars. The latter is potentially interesting as an acrylamide reduction strategy as the more fructose and glucose in potatoes when they are fried, the more acrylamide is formed. Read more here and here.
Watch a video from Friedberg explaining the technology in more detail below:
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